Compositions and methods for inhibiting expression of the MYC gene

• US 8,124,752 B2
• Filed: 07/09/2007
• Issued: 02/28/2012
• Est. Priority Date: 07/10/2006
• Status: Active Grant

• Current Assignee: Alnylam Pharmaceuticals Incorporated
• Original Assignee: Alnylam Pharmaceuticals Incorporated
• Inventors: Bumcrot, David, Bramlage, Birgit, Tan, Pamela
• Primary Examiner(s): Chong, Kimberly
• Application Number:
  US12/373,039
• Publication Number:
  US 20100016405A1
• Time in Patent Office: 1,695 Days
• Field of Search: None
• US Class Current: 536/24.5
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/3521 Methyl

Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the MYC gene (MYC gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the MYC gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by MYC gene expression and the expression of the MYC gene using the pharmaceutical composition.

Claims

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human MYC gene, wherein said dsRNA comprises a sense strand and an antisense strand, wherein the sense strand consists of the nucleotide sequence of SEQ ID NO:

11 and the antisense strand consists of the nucleotide sequence of SEQ ID NO;

12 and each strand is modified as follows to include a 2′

-O-methyl ribonucleotide as indicated by a lower case letter “

c”

or “

u” and

a phosphorothioate as indicated by a lower case letter “

s”

;

SEQ ID NO;

11 is cGAcGAGAAcAGuuGAAAcTsT and

SEQ ID NO;

12 is GUUUcAACUGUUCUCGUCGTsT.

2. A cell comprising the dsRNA of claim 1.

3. A pharmaceutical composition for inhibiting the expression of the MYC gene, comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.

4. An in-vitro method for inhibiting the expression of the MYC gene in a cell, the method comprising:

(a) introducing into the cell the dsRNA of claim 1; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of the MYC gene, thereby inhibiting expression of the MYC gene in the cell.

5. A vector for inhibiting the expression of the MYC gene, said vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of claim 1.

6. A cell comprising the vector of claim 4.

7. A method of treating breast cancer comprising administering to a patient in need of such treatment, a therapeutically effective amount of the dsRNA of claim 1.

8. The pharmaceutical composition of claim 3, wherein the carrier is lipid carrier.